Biophysical Society Bulletin | January 2024

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Know the Editor Sarah Rauscher University of Toronto Associate Editor Biophysical Reports

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Sarah Rauscher

At a cocktail party of non-scientists, how would you explain what you do? We look at proteins as a machine, and we are aiming to describe in precise detail how this machine works, to develop a blueprint. Viruses and bacteria, for example, target specific proteins and bind with them, while protein mutations are involved in diseases like cancer. Treatment design, therefore, often starts with getting a clear understanding of the structure and dynamics of the pro teins involved in disease. We are using computer simulations to better understand disordered proteins—proteins without a fixed, static structure. Computational methods are perfectly suited to studying the molecular structures of disordered proteins, which cannot be fully investigated through experiments. By simulating these proteins, in collaboration with people who are working on them by using experimental approaches, we can develop a more complete picture of what they look like and how they move. These simulations are computationally challenging and can take on the order of hundreds to thousands of computers for, in some cases, a full year. It took me eight months to run all the simula tions for my first PhD paper. As computational power increases, we can simulate larger systems for longer times. What are you currently working on that excites you? Changes in proteins are at the root of many diseases, and the structure and dynamics of proteins are highly sensitive to even subtle perturbations. For example, disordered proteins are af fected by changes in solution conditions, while protein mutations underlie various diseases. Simulations offer a powerful tool to describe the effects of different types of perturbations at the mo lecular level. My lab is currently working on several projects along these lines. For example, we are studying the effect of molecular crowding on the structure and dynamics of fluorescent proteins in collaboration with Eitan Lerner at the Hebrew University of Jerusalem. We are simulating protein motion in a crystal environ ment in collaboration with Rama Ranganathan at the University of Chicago. Through collaboration, we can relate molecular mecha nisms deciphered by using computational and in vitro approaches to biological processes in vivo, allowing us to make more rapid progress than any of these approaches could make individually.

Biophysical Reports Establishing Riboglow-FLIM to visualize noncoding RNAs inside live zebrafish embryos Nadia Sarfraz, Harrison J. Lee, Morgan K. Rice, Emilia Moscoso, Luke K. Shafik, Eric Glasgow, Suman Ranjit, Ben J. Lambeck, Esther Braselmann “The discovery of fluorescent proteins and subsequent engi neering efforts have revolutionized fields across biology, but comparable tools to visualize RNAs live are critically lacking. Here, the authors demonstrate that the RNA Riboglow-FLIM platform might fill this need. Of note, they establish that Riboglow-FLIM requires fluorescence lifetime imaging mi croscopy (FLIM). The fluorophore element in Riboglow-FLIM is variable, hence a far-red fluorophore for use in live multicel lular environments can be used after careful biophysical char acterization. The authors make use of the common strategy of injecting mammalian cells producing a fluorescence sensor into live embryos as a systematic step of introducing com plexity of a multicellular environment. The authors demon strate that different cellular conditions produce heteroge neous Riboglow-FLIM signatures that can be quantitatively differentiated.”

Version of Record Published September 25, 2023 DOI: https:/doi.org/10.1016/j.bpr.2023.100132

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